The present invention relates to 3,4-diaminopyridine derivatives, a process for preparing them and the use of these 3,4-diaminopyridine derivatives as catalysts.
Donor-substituted pyridines play a prominent role as nucleophilic catalysts in many synthetically important transformations such as the acylation of alcohols, amines or enolates. See, for example, G. Höfle, W. Steglich, H. Vorbrüggen, Angew. Chem. 1978, 90, 602-615; Angew. Chem. Int. Ed. Engl. 1978, 17, 569-583; E. F. V. Scriven, Chem. Soc. Rev. 1983, 12, 129-161; A. Hassner, in Encyclopedia of Reagents for Organic Synthesis, Wiley, Chichester, 1995, 2022-2024; U. Ragnarsson, L. Grehn, Acc. Chem. Res. 1998, 31, 494-501; A. C. Spivey, A. Maddaford, A. Redgrave, Org. Prep. Proced. Int. 2000, 32, 331-365; D. J. Berry, C. V. Digiovanna, S. S. Metrick, R. Murugan, Arkivoc 2001, 201-226; and A. C. Spivey, S. Arseniyadis, Angew. Chem. 2004, 116, 5552-5557; Angew. Chem. Int. Ed. Engl. 2004, 43, 5436-5441. Also see E. Vedejs, M. Jure, Angew. Chem. 2005, 117, 4040-4069; Angew. Chem. Int. Ed. Engl. 2005, 44, 3971-4001; P. I. Dalko, L. Moisan, Angew. Chem. 2004, 116, 5248-5286; Angew. Chem. Int. Ed. Engl. 2004, 43, 5138-5178. (c) G. Fu, Acc. Chem. Res. 2004, 37, 542-547; S. France, D. J. Guerin, S. J. Miller, T. Lectka, Chem. Rev. 2003, 103, 2985-3012; and A. C. Spivey, A. Maddaford, A. Redgrave, Org. Prep. Proced. Int. 2000, 32, 331-365. (f) G. Fu, Acc. Chem. Res. 2000, 33, 412-420.
Great progress has been achieved recently in kinetic racemate resolution experiments using appropriately substituted derivatives of (4-dimethylamino)pyridine 1 (DMAP) or (4-pyrrolidino)pyridine 2 (PPY) (See Scheme 1). Reports of this progress appear in T. Kawabata, R. Stragies, T. Fukaya, K. Fuji, Chirality 2003, 15, 71; T. Kawabata, R. Stragies, T. Fukaya, Y. Nagaoka, H. Schedel, K. Fuji, Tetrahedron Lett. 2003, 44, 1545; G. Priem, B. Pelotier, S. J. F. Macdonald, M. S. Anson, I. B. Campbell, J. Org. Chem. 2003, 68, 3844; B. Pelotier, G. Priem, S. J. F. Macdonald, M. S. Anson, R. J. Upton, I. B. Campbell, Tetrahedron Lett. 2005, 46, 9005; A. C. Spivey, T. Fekner, S. E. Spey, H. Adams, J. Org. Chem. 1999, 64, 9430, and literature cited there; A. C. Spivey, T. Fekner, S. E. Spey, J. Org. Chem. 2000, 65, 3154; A. C. Spivey, A. Maddafort, T. Fekner, A. J. Redgrave, C. S. Frampton, J. Chem. Soc. Perkin Trans. 1. 2000, 3460; A. C. Spivey, A. Maddafort, T. Fekner, D. P. Leese, A. J. Redgrave, C. S. Frampton, J. Chem. Soc. Perkin Trans. 1, 2001, 1785; C. Malardier-Jugroot, A. C. Spivey, M. A. Whitehead, J. Mol. Struct. (THEOCHEM) 2003, 623, 263; A. C. Spivey, D. P. Leese, F. Zhu, S. G. Davey, R. L. Jarvest, Tetrahedron 2004, 60, 4513; A. C. Spivey, S. Arseniyadis, T. Fekner, A. Maddaford, D. P. Lees, Tetrahedron 2006, 62, 295; C. O. Dalaigh, S. J. Hynes, D. J. Maher, S. J. Connon, Org. Biomol. Chem. 2005, 3, 981; C. O. Dalaigh, S. J. Hynes, J. E. O'Brien, T. McCabe, D. J. Maher, G. W. Watson, S. J. Connon, Org. Biomol. Chem. 2006, 4, 2785; S. A. Shaw, P. Aleman, E. Vedejs, J. Am. Chem. Soc. 2003, 125, 13368-13369; S. A. Shaw, P. Aleman, J. Christy, J. W. Kampf, P. Va, E. Vedejs, J. Am. Chem. Soc. 2006, 128, 925-934; and S. Yamada, T. Misono, Y. Iwai, Tet. Lett 2005, 46, 2239.
Despite these developments, the field remains somewhat unbalanced, with a variety of solutions being available for particular synthetic problems such as kinetic racemate resolution of secondary alcohols but other apparently similar challenges such as kinetic racemate resolution of primary or tertiary alcohols appearing virtually insoluble.

In this situation, a modular catalyst concept which allows a broad range of structural variations within a single synthesis strategy appears highly desirable. Concepts of this type have been researched recently by Miller et al. for catalysts which are based on peptidic structures and use imidazole as active center. See for, example, S. J. Miller, Acc. Chem. Res. 2004, 37, 601-610, and references therein; M. B. Fierman, D. J. O'Leary, W. E. Steinmetz, S. J. Miller, J. Am. Chem. Soc. 2004, 126, 6967-6971; J. W. Evans, M. B. Fierman, S. J. Miller, J. A. Ellman, J. Am. Chem. Soc. 2004, 126, 8134-8135; B. R. Sculimbrene, Y. Xu, S. J. Miller, J. Am. Chem. Soc. 2004, 126, 13182-13183; A. J. Morgan, Y. K. Wang, M. F. Roberts, S. J. Miller, J. Am. Chem. Soc. 2004, 126, 15370-15371; C. A. Lewis, B. R. Sculimbrene, Y. Xu, S. J. Miller, Org. Lett. 2005, 3021; Y. Xu, B. R. Sculimbrene, S. J. Miller, J. Org. Chem. 2006, 71, 4919-4928; and S. France, D. J. Guerin, S. J. Miller, T. Lectka, Chem. Rev. 2003, 103, 2985-3012.
Peptides are also the variable structural element in PPY derivatives developed by Kawabata et al. and by Campbell et al. See, e.g., T. Kawabata, R. Stragies, T. Fukaya, K. Fuji, Chirality 2003, 15, 71; T. Kawabata, R. Stragies, T. Fukaya, Y. Nagaoka, H. Schedel, K. Fuji, Tetrahedron Lett. 2003, 44, 1545; G. Priem, B. Pelotier, S. J. F. Macdonald, M. S. Anson, I. B. Campbell, J. Org. Chem. 2003, 68, 3844; B. Pelotier, G. Priem, S. J. F. Macdonald, M. S. Anson, R. J. Upton, I. B. Campbell, Tetrahedron Lett. 2005, 46, 9005. In all of these cases, the peptidic structures influence the course of the reaction by means of additional catalysts which are built up between substrates and the side chains in the rate-determining step of the catalysis cycle. However, the electronic character of the nucleophilic catalysis center is generally not altered by the variations of the peptide structures.
The modular construction of 3-substituted derivatives of 1 and 2, on the other hand, has the potential to modify both the nucleophilicity of the pyridine ring and also its side asymmetry. Experiments carried out to date have been restricted to examining stereodifferentiating processes.
Earlier studies on the catalytic potential of donor-substituted pyridines in acylation reactions have already indicated the relative stability of acylpyridinium cations 4Ac as qualitative criterion for the catalytic activity. See, for example, M. R. Heinrich, H. S. Klisa, H. Mayr, W. Steglich, H. Zipse, Angew. Chem. 2003, 115, 4975-4977; Angew. Chem. Int. Ed. 2003, 42, 4826-4828; and I. Held, A. Villinger, H. Zipse, Synthesis 2005, 1425-1426.
